Targeted protein kinase A and PP-2B regulate insulin secretion through reversible phosphorylation

Linda B. Lester, Maree C. Faux, J. Brian Nauert, John D. Scott

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Protein kinases and phosphatases play key roles in integrating signals from various insulin secretagogues. In this study, we show that the activities of the cAMP-dependent protein kinase (PKA) and the calcium/calmodulin-dependent phosphatase. PP-2B are coordinated resulting in the regulation of insulin secretion. Transient inhibition of PP-2B, using the immunosuppressant FK506, increased forskolin stimulated insulin secretion by 2.5-fold ± 0.3 (n = 6) in rat islets and RINm5F cells. Surprisingly, forskolin treatment resulted in the dephosphorylation of the vesicle-associated protein synapsin 1 and increased PP-2B activity by 2.98 ± 0.97-fold (n = 4). One potential explanation for the observed coordination of PKA and PP-2B activity is their colocalization through a mutual anchoring protein. AKAP79/ 150. Accordingly, RINm5F cells expressing AKAP79 exhibited decreased insulin secretion, reduced PP-2B activity and were insensitive to FK506. This suggests that AKAP targeting of PKA and PP-2B maintains a signal transduction complex that may regulate reversible phosphorylation events involved in insulin secretion.

Original languageEnglish (US)
Pages (from-to)1218-1227
Number of pages10
JournalEndocrinology
Volume142
Issue number3
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Endocrinology

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